1. Field of the Invention:
This invention is related to diagnostic assays for the detection of antigens in blood and particularly to diagnostic assays relating to the detection of antigens associated with breast cancer.
2. Description of the Prior Art:
Carcinoma of the breast is the most frequent form of cancer in women in North America and Europe. The traditional diagnostic technique of palpation is often insuffient for the detection of early lesions. Often, by the time that a malignant mass becomes distinguishable from a benign nodule of breast tissue, the cancer has metastasized. The principal alternative merhod of detecting breast malignancies in recent years is the mammogram, a low-voltage X-ray procedure. However, because of the oncogenic potential of this X-ray procedure, the method is of limited usefulness in premenopausal women. Current guidelines of the National Cancer Institute recommend that routine mammography be restricted to women over 50 and to high-risk patients under 50. There accordingly remains a need for a non-invasive method of detecting early malignancies of the breast.
One method of detecting cancer which has received considerable attention in recent years is the use of immunological techniques for detecting antigens associated with cancers. The best known such antigen is carcinoembryonic antigen (CEA). When first discovered, CEA was thought to be specific to cancers of the digestive system. However, CEA has since been detected in normal adults as well as in patients with benign liver disease, such as alcoholic hepatitis or biliary obstruction. Because of the overall lack of specificity and sensitivity, there being no threshold difference in CEA levels that serves to separate benign from malignant conditions, CEA cannot be used as a general diagnostic test. It is principally used in the monitoring of response to treatment.
Similar antigens are now known to exisr in breast cancer. Breast tissue markers such as casein [Franchimont et al, Cancer, 39, 2806-2812 (1977)] and .alpha.-lactalbumin [Kleinberg et al, Science, 190, 276-278 (1975)] and proported cancer markers such as glycosyl transferases [Ip et al, Cancer Res., 38, 723-728 (1978); Dao et al, J. Natl. Cancer Inst., 65, 529-534 (1980)], glycolipids [Kloppel et al, Proc. Natl. Acad. Sci. USA, 74, 3011-3013 (1977)], and phospholipids [Skipsky et al, Proc. Soc. Exp. Biol. Med., 136, 1261-1264 (1971)] have all been used in various diagnostic techniques for breast cancer without gaining widespread acceptance as a breast cancer marker. More recently, circulating human mammary epithelial antigens have been proposed as specific markers for breast cancer [Ceriani et al, Proc. Natl. Acad. Sci. USA, 79, 5420-5424 (1982)].
However, one recurring problem in the immunological detection of any antigen present in blood (not just in tests for antigens associated with cancer) is the occurrence of false positive and false negative reactions. For example, in the area of cancer diagnosis, false positives can result in unnecessary diagnostic surgery or mammography of a patient who does not have cancer, while false negatives result in cancer that goes undetected. Accordingly, a method for improving the discrimination of immunological assays and eliminating false positives and false negatives to the maximum extent possible is needed both in the general area of antigen detection and particularly in the detection of life-threatening malignancies.